tbuckley/cabot-search huggingface dataset:
A Cell-Fate Reprogramming Strategy Reverses Epithelial-to-Mesenchymal Transition of Lung Cancer Cells While Avoiding Hybrid States
Authors: Namhee Kim, Chae Young Hwang, Taeyoung Kim, Hyunjin Kim, Kwang-Hyun Cho
Journal: Cancer Research (2023)

Abstract The epithelial-to-mesenchymal transition (EMT) of primary cancer contributes to the acquisition of lethal properties, including metastasis and drug resistance. Blocking or reversing EMT could be an effective strategy to improve cancer treatment. However, it is still unclear how to achieve complete EMT reversal (rEMT), as cancer cells often transition to hybrid EMT states with high metastatic potential. To tackle this problem, we employed a systems biology approach and identified a core-regulatory circuit that plays the primary role in driving rEMT without hybrid properties. Perturbation of any single node was not sufficient to completely revert EMT. Inhibition of both SMAD4 and ERK signaling along with p53 activation could induce rEMT in cancer cells even with TGFβ stimulation, a primary inducer of EMT. Induction of rEMT in lung cancer cells with the triple combination approach restored chemosensitivity. This cell-fate reprogramming strategy based on attractor landscapes revealed potential therapeutic targets that can eradicate metastatic potential by subverting EMT while avoiding hybrid states. Significance: Network modeling unravels the highly complex and plastic process regulating epithelial and mesenchymal states in cancer cells and discovers therapeutic interventions for reversing epithelial-to-mesenchymal transition and enhancing chemosensitivity.
Baseline 18F-FDG Metabolic Tumor Volume Predicts Response to Rituximab Induction in Post-transplant Lymphoproliferative Disorders: A Multi-institutional Retrospective Study
Authors: David Morland, Lukshe Kanagaratnam, Fabrice Hubelé, Elise Toussaint, Sylvain Choquet, Aurélie Kas, Pierre-Ambroise Caquot, Corinne Haioun, Emmanuel Itti, Stéphane Leprêtre, Pierre Decazes, Fontanet Bijou, Paul Schwartz, Caroline Jacquet, Adrien Chauchet, Julien Matuszak, Nassim Kamar, Pierre Payoux, Eric Durot
Journal: HemaSphere (2023)

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of immunosuppression. Sequential treatment is commonly proposed, combining induction with rituximab (R-induction) followed by either continuation of treatment or addition of chemotherapy depending on response. Response to R-induction, often assessed by CT scan, is a major predictor of overall survival (OS). The aim of the study was to analyze predictive factors of R-induction response, including total metabolic tumor volume (TMTV), and investigate the role of 18F-FDG PET/CT in response assessment. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. Only patients treated by R-induction with a baseline 18F-FDG PET/CT were included. Response to R-induction was assessed by 18F-FDG PET/CT. The optimal threshold of TMTV for rituximab response was determined using receiver operating characteristic curves. Univariate and multivariate analyses were conducted to identify predictive factors of response. A total of 67 patients were included. Survival characteristics were similar to those previously reported: the complete response rate to R-induction was 30%, the 3-year OS estimate was 66%, and the treatment-related mortality was 4%. The optimal threshold for TMTV to predict R-induction response was 135 cm3. The response rate to R-induction was 38% in the 21 patients with TMTV ≥ 135 cm3 and 72% in the 46 patients with TMTV < 135 cm3. TMTV was a significant predictor of response, both at univariate and multivariate analyses (odd ratios = 3.71, P = 0.022). Baseline TMTV is predictive of response to R-induction. Early assessment of patient response is feasible with 18F-FDG PET/CT.
Adoption of Point-of-Use Chlorination for Household Drinking Water Treatment: A Systematic Review
Authors: Yoshika S. Crider, Miki Tsuchiya, Magnifique Mukundwa, Isha Ray, Amy J. Pickering
Journal: Environmental Health Perspectives (2023)

Background: Centralized chlorination of urban piped water supplies has historically contributed to major reductions in waterborne illness. In locations without effective centralized water treatment, point-of-use (POU) chlorination for households is widely promoted to improve drinking water quality and health. Realizing these health benefits requires correct, consistent, and sustained product use, but real-world evaluations have often observed low levels of use. To our knowledge, no prior reviews exist on adoption of chlorine POU products. Objectives: Our objectives were to identify which indicators of adoption are most often used in chlorine POU studies, summarize levels of adoption observed, understand how adoption changes over time, and determine how adoption is affected by frequency of contact between participants and study staff. Methods: We conducted a systematic review of household POU chlorination interventions or programs from 1990 through 2021 that reported a quantitative measure of adoption, were conducted in low- and middle-income countries, included data collection at households, and reported the intervention start date. Results: We identified 36 studies of household drinking water chlorination products that met prespecified eligibility criteria and extracted data from 46 chlorine intervention groups with a variety of chlorine POU products and locations. There was no consensus definition of adoption of household water treatment; the most common indicator was the proportion of household stored water samples with free chlorine residual &gt;0.1 or 0.2mg/L. Among studies that reported either free or total chlorine–confirmed adoption of chlorine POU products, use was highly variable (across all chlorine intervention groups at the last time point measured in each study; range: 1.5%–100%; sample size-weighted median=47%; unweighted median=58%). The median follow-up duration among intervention groups was 3 months. On average, adoption declined over time and was positively associated with frequency of contact between respondents and study staff. Discussion: Although prior research has shown that POU chlorine products improve health when correctly and consistently used, a reliance on individual adoption for effective treatment is unlikely to lead to the widespread public health benefits historically associated with pressurized, centralized treatment of piped water supplies. https://doi.org/10.1289/EHP10839
Detection of colon cancer recurrences during follow-up care by general practitioners vs surgeons
Authors: Julien A M Vos, Edanur Sert, Wim B Busschers, Laura A M Duineveld, Thijs Wieldraaijer, Jan Wind, Sandra C Donkervoort, Marc J P M Govaert, Frédérique H Beverdam, Anke B Smits, Willem A Bemelman, Gijsbert Heuff, Henk C P M van Weert, Kristel M van Asselt, A A W van Geloven, A W H van de Ven
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background In the I CARE study, colon cancer patients were randomly assigned to receive follow-up care from either a general practitioner (GP) or a surgeon. Here, we address a secondary outcome, namely, detection of recurrences and effect on time to detection of transferring care from surgeon to GP. Methods Pattern, stage, and treatment of recurrences were described after 3 years. Time to event was defined as date of surgery, until date of recurrence or last follow-up, with death as competing event. Effects on time to recurrence and death were estimated as hazard ratios (HRs) using Cox regression. Restricted mean survival times were estimated. Results Of 303 patients, 141 were randomly assigned to the GP and 162 to the surgeon. Patients were male (67%) with a mean age of 68.0 (8.4) years. During follow-up, 46 recurrences were detected; 18 (13%) in the GP vs 28 (17%) in the surgeon group. Most recurrences were detected via abnormal follow-up tests (74%) and treated with curative intent (59%). Hazard ratio for recurrence was 0.75 (95% confidence interval [CI] = 0.41 to 1.36) in GP vs surgeon group. Patients in the GP group remained in the disease-free state slightly longer (2.76 vs 2.71 years). Of the patients, 38 died during follow-up; 15 (11%) in the GP vs 23 (14%) in the surgeon group. Of these, 21 (55%) deaths were related to colon cancer. There were no differences in overall deaths between the groups (HR = 0.76, 95% CI = 0.39 to 1.46). Conclusion Follow-up provided by GPs vs surgeons leads to similar detection of recurrences. Also, no differences in mortality were found.
Interim Positron Emission Tomography During Frontline Chemoimmunotherapy for Follicular Lymphoma
Authors: Reid W. Merryman, Laure Michaud, Robert Redd, Patrizia Mondello, Hyesun Park, Gabriela Spilberg, Matthew Robertson, Eleanor Taranto, Gulrayz Ahmed, Matthew Chase, Erin Jeter, Inhye E. Ahn, Jennifer R. Brown, Jennifer Crombie, Matthew S. Davids, David C. Fisher, Eric Jacobsen, Caron A. Jacobson, Austin I. Kim, Ann S. LaCasce, Samuel Y. Ng, Oreofe O. Odejide, Erin M. Parry, Gilles Salles, Andrew D. Zelenetz, Philippe Armand, Heiko Schöder, Heather Jacene
Journal: HemaSphere (2023)

While most patients with follicular lymphoma (FL) have excellent outcomes with frontline chemoimmunotherapy (CIT), a subset of patients will experience early progression, which is associated with poor subsequent outcomes. Novel biomarkers are needed to identify high-risk patients earlier. We hypothesized that interim positron emission tomography (PET) would predict progression-free survival (PFS) in this population. We retrospectively identified 128 patients with grade 1–3A FL who had an interim PET after 2–4 cycles of frontline CIT at 2 academic centers. PET scans were analyzed using Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Interim PET DS was a significant predictor of PFS ( P &lt; 0.003). Patients with a DS of 3 had outcomes similar to those of patients with a DS of 4, so were categorized as PET-positive for additional analyses. Interim PET remained a strong predictor of PFS (DS 3-5, hazard ratio [HR] 2.4, P = 0.006) in a multivariable analysis and was also an early predictor of both a positive end-of-treatment PET ( P &lt; 0.001) and progression of disease within 24 months (POD24) ( P = 0.006). An optimal ΔSUVmax cutoff of 75% was selected using the bootstrap method. ΔSUVmax &lt;75% was also a significant predictor of PFS on univariable and multivariable analyses (HR 2.8, P &lt; 0.003). In a separate cohort of 50 patients with high-grade FL, interim PET interpreted using either DS ( P &lt; 0.001) or ΔSUVmax75% ( P = 0.034) was also a significant predictor of inferior PFS. In conclusion, interim PET is an independent predictor of PFS and may be useful as a tool for response-adapted treatment strategies in FL.
Impact of the polymer backbone chemistry on interactions of amino-acid-derived zwitterionic polymers with cells
Authors: Meike N. Leiske, Bruno G. De Geest, Richard Hoogenboom
Journal: Bioactive Materials (2023)

Zwitterionic polymers are known to interact with cells and have been shown to reveal cancer cell specificity. In this work, the importance of the chemistry of the polymer backbone for the cellular specificity of amino-acid-derived polyzwitterions is demonstrated. A series of glutamic acid (Glu)-based vinyl monomers (
Efficacy of Elimination Diets in Eosinophilic Esophagitis: A Systematic Review and Meta-analysis
Authors: Christoph Mayerhofer, Anna Maria Kavallar, Denise Aldrian, Andrea Katharina Lindner, Thomas Müller, Georg Friedrich Vogel
Journal: Clinical Gastroenterology and Hepatology (2023)

<h3>Background & Aims</h3> Eosinophilic esophagitis (EoE) can be treated by proton pump inhibitors, topical corticosteroids, or dietary measures. This study systematically assessed the efficacy of 4 major dietary treatment regimens in EoE, updating the evidence presented in a meta-analysis from 2014. <h3>Methods</h3> Electronic databases such as PubMed, Scopus, and Web of Science, and other sources were searched up to September 2022 to identify studies on dietary treatment of EoE. Based on histologic remission criteria, the efficacy of these treatments was pooled and analyzed with respect to the type of dietary regimen: 6-food elimination diet (SFED), 4-food elimination diet (FFED), 1-food elimination diet (OFED), and a targeted elimination diet (TED). Clinical response rates, food sensitization, and efficacies for a pediatric subpopulation were calculated. Influencing variables on efficacies were estimated via meta-regression analyses. <h3>Results</h3> Thirty-four studies with 1762 patients met the inclusion criteria. The overall rate of histologic remission was 53.8% (95% CI, 48.0%–59.6%), and in the individual dietary groups was 61.3% (95% CI, 53.0%–69.3%) for SFED, 49.4% (95% CI, 32.5%–66.3%) for FFED, 51.4% (95% CI, 42.6%–60.1%) for OFED, and 45.7% (95% CI, 32.0%–59.7%) for TED. Dietary regimen and patient age did not significantly affect rates of histologic remission. The overall rate of clinical response was 80.8% (95% CI, 72.3%–88.2%), with response rates of 92.8% (95% CI, 81.2%–99.6%) for SFED, 74.1% (95% CI, 49.8%–92.6%) for FFED, 87.1% (95% CI, 58.4%–99.9%) for OFED, and 69.0% (95% CI, 50.2%85.3%) for TED. <h3>Conclusions</h3> Dietary therapy is an effective treatment for EoE patients of any age. The current results could support a trend toward less-restrictive dietary regimens as a primary treatment option.
Adalimumab in Biologic-naïve Patients With Crohn’s Disease After Resolution of an Intra-abdominal Abscess: A Prospective Study From the GETAID
Authors: Yoram Bouhnik, Guillaume Pineton de Chambrun, Jérôme Lambert, Maria Nachury, Philippe Seksik, Romain Altwegg, Lucine Vuitton, Carmen Stefanescu, Stéphane Nancey, Alexandre Aubourg, Mélanie Serrero, Jérôme Filippi, Kristell Desseaux, Stéphanie Viennot, Vered Abitbol, Madina Boualit, Arnaud Bourreille, Cyrielle Giletta, Anthony Buisson, Xavier Roblin, Nina Dib, Georgia Malamut, Aurélien Amiot, Mathurin Fumery, Edouard Louis, Yasmine Elgharabawy, Laurent Peyrin-Biroulet, Jacques Moreau, Xavier Treton, Charlotte Mailhat, Justine Pollet, Carole Martins, Guillaume Savoye, Noémie Tavernier, Jean-Yves Mary, Magali Zappa, Claire Painchart
Journal: Clinical Gastroenterology and Hepatology (2023)
Saroglitazar, a Dual PPAR α/γ Agonist, Improves Atherogenic Dyslipidemia in Patients With Non-Cirrhotic Nonalcoholic Fatty Liver Disease: A Pooled Analysis
Authors: Mohammad Shadab Siddiqui, Deven Parmar, Farheen Sheikh, Shiv Kumar Sarin, Laura Cisneros, Samer Gawrieh, Taufik Momin, Ajay Duseja, Arun J. Sanyal
Journal: Clinical Gastroenterology and Hepatology (2023)
Early humoral response to COVID-19 vaccination in patients living with obesity and diabetes in France. The COVPOP OBEDIAB study with results from the ANRS0001S COV-POPART cohort
Authors: Bénédicte Gaborit, Sara Fernandes, Paul Loubet, Laetitia Ninove, Anne Dutour, Bertrand Cariou, Muriel Coupaye, Karine Clement, Sébastien Czernichow, Claire Carette, Noémie Resseguier, Laure Esterle, Sabrina Kali, Marie Houssays, Xavier de Lamballerie, Linda Wittkop, Odile Launay, Martine Laville
Journal: Metabolism (2023)
Reduction of anaerobic glycolysis contributes to angiotensin II-induced podocyte injury with foot process effacement
Authors: Zhaowei Chen, Zijing Zhu, Wei Liang, Zilv Luo, Jijia Hu, Jun Feng, Zongwei Zhang, Qiang Luo, Hongxia Yang, Guohua Ding
Journal: Kidney International (2023)
Mesenchymal Stem Cells Sense the Toughness of Nanomaterials and Interfaces
Authors: Lihui Peng, Carlos Matellan, Minerva Bosch‐Fortea, Jordi Gonzalez‐Molina, Matteo Frigerio, Stefan Salentinig, Armando del Rio Hernandez, Julien E. Gautrot
Journal: Advanced Healthcare Materials (2023)

Abstract Stem cells are known to sense and respond to the mechanical properties of biomaterials. In turn, cells exert forces on their environment that can lead to striking changes in shape, size and contraction of associated tissues, and may result in mechanical disruption and functional failure. However, no study has so far correlated stem cell phenotype and biomaterials toughness. Indeed, disentangling toughness‐mediated cell response from other mechanosensing processes has remained elusive as it is particularly challenging to uncouple Youngs' or shear moduli from toughness, within a range relevant to cell‐generated forces. In this report, it is shown how the design of the macromolecular architecture of polymer nanosheets regulates interfacial toughness, independently of interfacial shear storage modulus, and how this controls the expansion of mesenchymal stem cells at liquid interfaces. The viscoelasticity and toughness of poly( l ‐lysine) nanosheets assembled at liquid‐liquid interfaces is characterised via interfacial shear rheology. The local (microscale) mechanics of nanosheets are characterised via magnetic tweezer‐assisted interfacial microrheology and the thickness of these assemblies is determined from in situ ellipsometry. Finally, the response of mesenchymal stem cells to adhesion and culture at corresponding interfaces is investigated via immunostaining and confocal microscopy.
Infection rates of 70% of the population observed within 3 weeks after release of COVID-19 restrictions in Macao, China
Authors: Jingyi Liang, Ruibin Liu, Wei He, Zhiqi Zeng, Yangqianxi Wang, Boyuan Wang, Lixi Liang, Tong Zhang, C.L. Philip Chen, ChiWai Chang, Chitin Hon, Eric H.Y. Lau, Zifeng Yang, KaLok Tong
Journal: Journal of Infection (2023)
Intravenous paracetamol for persistent pain after endoscopic mucosal resection discriminates patients at risk of adverse events and those who can be safely discharged
Authors: Lobke Desomer, David J. Tate, Leshni Pillay, Halim Awadie, Mayenaaz Sidhu, Golo Ahlenstiel, Michael J. Bourke
Journal: Endoscopy (2023)

Introduction The frequency and severity of abdominal pain after endoscopic mucosal resection (EMR) of colonic laterally spreading lesions (LSLs) of ≥ 20 mm is unknown, as are the risk factors to predict its occurrence. We aimed to prospectively characterize pain after colonic EMR , determine the rapidity and frequency of its resolution after analgesia, and estimate the frequency of needing further intervention. Methods Procedural and lesion data on consecutive patients with LSLs who underwent EMR at a single tertiary referral center were prospectively collected. If pain after colonic EMR, graded using a visual analogue scale (VAS), lasted &gt; 5 minutes, 1 g of paracetamol was administered. Pain lasting &gt; 30 minutes lead to clinical review and upgrade to opiate analgesics. Investigations and interventions for pain were recorded. Results 67/336 patients (19.9 %, 95 %CI 16.0 %–24.5 %) experienced pain after colonic EMR (median VAS 5, interquartile range 3–7). Multivariable predictors of pain were: lesion size ≥ 40 mm, odds ratio [OR] 2.15 (95 %CI 1.22–3.80); female sex, OR 1.99 (95 %CI 1.14–3.48); and intraprocedural bleeding requiring endoscopic control, OR 1.77 (95 %CI 0.99–3.16). Of 67 patients with pain, 51 (76.1 %, 95 %CI 64.7 %–84.7 %) had resolution of their “mild pain” after paracetamol and were discharged without sequelae. The remaining 16 (23.9 %) required opiate analgesia (fentanyl), after which 11/16 patients (68.8 %; “moderate pain”) could be discharged. The 5/67 patients (7.5 %) with “severe pain” had no resolution despite fentanyl; all settled during hospital admission (median duration 2 days), intravenous analgesia, and antibiotics. Conclusion Pain after colonic EMR occurs in approximately 20 % of patients and resolves rapidly and completely in the majority with administration of intravenous paracetamol. Pain despite opiates heralds a more serious scenario and further investigation should be considered.
Skeletal “Superscan” With 11C-Methionine PET/CT in Polycythemia Vera
Authors: Mads Ryø Jochumsen, Michael Alle Madsen, Anne Kirstine Arveschoug
Journal: Clinical Nuclear Medicine (2023)

11 C-methionine PET/CT for parathyroid adenoma localization on a 60-year-old woman known with polycythemia vera revealed highly methionine-avid red bone marrow, an uptake pattern that has previously been described in hematological disease such as multiple myeloma. An equivalent skeletal "superscan" pattern in polycythemia vera has been described with other PET tracers, but this case illustrates that this pattern can be seen with 11 C-methionine PET/CT as well and can be added to the list of potential pitfalls.
Planning for Mpox on a College Campus: A Model-Based Decision-Support Tool
Authors: Alexandra Savinkina, Melanie Chitwood, Jiye Kwon, Virginia E. Pitzer, Gregg Gonsalves, A. David Paltiel
Journal: Annals of Internal Medicine (2023)

Background: In spring and summer 2022, an outbreak of mpox occurred worldwide, largely confined to men who have sex with men (MSM). There was concern that mpox could break swiftly into congregate settings and populations with high levels of regular frequent physical contact, like university campus communities. Objective: To estimate the likelihood of an mpox outbreak and the potential effect of mitigation measures in a residential college setting. Design: A stochastic dynamic SEIR (susceptible, exposed but not infectious, infectious, or recovered) model of mpox transmission in a study population was developed, composed of: a high-risk group representative of the population of MSM with a basic reproductive number (R 0) of 2.4 and a low-risk group with an R 0 of 0.8. Base input assumptions included an incubation time of 7.6 days and time to recovery of 21 days. Setting: U.S. residential college campus. Participants: Hypothetical cohort of 6500 students. Intervention: Isolation, quarantine, and vaccination of close contacts. Measurements: Proportion of 1000 simulations producing sustained transmission; mean cases given sustained transmission; maximum students isolated, quarantined, and vaccinated. All projections are estimated over a planning horizon of 100 days. Results: Without mitigation measures, the model estimated an 83% likelihood of sustained transmission, leading to an average of 183 cases. With detection and isolation of 20%, 50%, and 80% of cases, the average infections would fall to 117, 37, and 8, respectively. Reactive vaccination of contacts of detected cases (assuming 50% detection and isolation) reduced mean cases from 37 to 17, assuming 20 vaccinated contacts per detected case. Preemptive vaccination of 50% of the high-risk population before outbreak reduced cases from 37 to 14, assuming 50% detection and isolation. Limitation: A model is a stylized portrayal of behavior and transmission on a university campus. Conclusion: Based on our current understanding of mpox epidemiology among MSM in the United States, this model-based analysis suggests that future outbreaks of mpox on college campuses may be controlled with timely detection and isolation of symptomatic cases. Primary Funding Source: National Institutes of Health National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases.